The Assessing Long Term Outcomes in Living Kidney Donors (ALTOLD) multicenter/multisite study successfully enrolled 200 pairs of living kidney donors and equally healthy two-kidney controls starting in July 2006. ALTOLD measured iohexol glomerular filtration rate (GFR) and traditional cardiovascular disease (CVD) risk factors pre- and 6, 12, 24 and 36 months post-donation. ALTOLD continues to answer important questions regarding the safety and the science of living kidney donation not addressed in previous uncontrolled cross- sectional studies. Important preliminary short-term results include the fact that GFR (slopes) increased between 6 and 36 months in donors v. controls, and that serum parathyroid hormone and uric acid levels have increased in donors v. controls. It is critically important to maintain these valuable cohorts to continue measuring trends in GFR and traditional CVD risk factors, and address new questions. The current proposal will conduct 6-year and begin 9-year follow-up visits. Long-term follow up will allow us to confirm the safety of kidney donation, and allow us to address a number of important scientific questions that have broad implications in our understanding of chronic kidney disease (CKD). ALTOLD will help determine whether the abnormalities associated CKD in observational studies are the cause or the result of the CKD. ALTOLD will test the hypothesis that GFR declines with age in normal, healthy individuals, and that unilateral nephrectomy accelerates this decline (Aim 1). It will also test the hypothesis that mild reductions in kidney function lead to chronic changes in mineral and bone disorders and other key CKD biomarkers in kidney donors (Aim 2). Finally, ALTOLD will test the hypothesis that mild declines in GFR affect arterial compliance (Aim 3). Specifically ALTOLD will measure aortic pulse wave velocity, which has been shown to correlate with CVD in patients with CKD, as well as small and large artery elasticity using applanation tonometry at the 6-year visit in both donors and controls. In summary, it is critical to capitalize on the short term investment in ALTOLD with uninterrupted long-term follow up that will minimize participant dropout and maximize the knowledge we will gain from this valuable cohort. PUBLIC HEALTH RELEVANCE: Previous studies have examined the effects of living kidney donation on donors, but have failed to compare donors to individuals with two kidneys who are equally healthy. As a result, some important effects of kidney donation could have gone undetected. The current study proposes to continue testing kidney function and heart disease risk in a group of kidney donors who have been paired with healthy two-kidney controls over an extended period of time.